title: Cytokine expression in tumors treated with donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  Risk factors for disease relapse are remaining tumor or leukemic cells or mixed chimerism (MC) following allogeneic hematopoietic stem cell transplantation. Donor lymphocyte infusion (DLI) after stem cell transplantation can contribute to complete donor chimerism and graft-versus-tumor/leukemia effect. We evaluate cytokine secretion at the single-cell level using ELISpot in relation to DLI effect on disease response.
  
  
  METHODS
  Blood samples were collected from four patients with solid tumors and four with hematological malignancies before DLI, and 1 and 3 weeks after DLI. Tumor response was evaluated according to the international Response Evaluation Criteria In Solid Tumors (RECIST) method. Indications for DLI were stable disease or MC and/or progressive disease in solid tumors, and molecular or early relapse, or MC in hematological malignancies. ELISpot was performed for TNF-α, IFN-γ, IL-12, IL-4, IL-10 and IL-13 cytokines.
  
  
  RESULTS
  Depending on the disease response, patients were divided into two groups: responders and nonresponders. Responders were patients who achieved partial response (one renal cell cancer) or stable disease (one prostate cancer) or clinical remission (two acute myeloid leukemia). Patients who relapsed, progressed or rejected the graft were the nonresponders. DLI rescued the renal cell cancer patient, who has partial response, and two acute myeloid leukemia patients, who are in clinical remission. Patients who responded tended to have a higher expression of TNF-α, IFN-γ, IL-12 and IL-10 than those who did not respond.
  
  
  CONCLUSIONS
  DLI can act when the patients' mononuclear cells have normal or increased capacity to produce TNF-α, IFN-γ, IL-12 and IL-10. Assessment of these cytokines may be useful to predict those patients who will respond to DLI therapy.
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital Huddinge F79, Stockholm, Sweden.
authors.forename: Réka
authors.initials: R
authors.lastname: Conrad
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Kerstin
authors.initials: K
authors.lastname: Cederlund
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Barkholt
mesh_terms: D046528:Chimerism; D058501:Enzyme-Linked Immunospot Assay; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma